Packaging solutions

ABSTRACT

A packaging system for storing ophthalmic devices such as contact lenses and methods for packaging such ophthalmic devices with solutions is disclosed. The packaging system contains an unused, ophthalmic device in an aqueous packaging solution comprising tris(hydroxymethyl)aminomethane or a salt thereof; wherein the solution has an osmolality of at least about 200 mOsm/kg and a pH in the range of about 6 to about 9.

BACKGROUND 1. Technical Field

The present invention generally relates to packaging solutions forophthalmic devices such as contact lenses.

2. Description of Related Art

Blister-packs and glass vials are typically used to individually packageeach soft contact lens for sale to a customer. Saline or deionized wateris commonly used to store the lens in the blister-packs, as mentioned invarious patents related to the packaging or manufacturing of contactlenses. Because lens material may tend to stick to itself and to thelens package, packaging solutions for blister-packs have sometimes beenformulated to reduce or eliminate lens folding and sticking.

It is highly desirable that contact lens be as comfortable as possiblefor wearers. Manufacturers of contact lenses are continually working toimprove the comfort of the lenses. Nevertheless, many people who wearcontact lenses still experience dryness or eye irritation throughout theday and particularly towards the end of the day. It has been stated thatif a lens is thoroughly cleaned before insertion, lacrimal fluid canadequately wet the lens. However, an insufficiently wetted lens at anypoint in time will cause significant discomfort to the lens wearer.Although wetting drops can be used as needed to alleviate suchdiscomfort, it would certainly be desirable if such discomfort did notarise in the first place.

It would be desirable to provide an improved packaging system forophthalmic devices such as a contact lens such that the lens would becomfortable to wear in actual use and allow for extended wear of thelens without irritation or other adverse effects to the cornea.

SUMMARY

In accordance with one embodiment of the present invention, a packagingsystem for the storage of an ophthalmic device comprising a sealedcontainer that contains an unused, ophthalmic device in an aqueouspackaging solution comprising tris(hydroxymethyl)aminomethane or a saltthereof; wherein the solution has an osmolality of at least about 200mOsm/kg and a pH in the range of about 6 to about 9.

In accordance with a second embodiment of the present invention, amethod of preparing a package comprising a storable, sterile ophthalmicdevice is provided comprising:

(a) immersing an ophthalmic device in an aqueous packaging solutioncomprising tris(hydroxymethyl)aminomethane or a salt thereof; whereinthe solution has an osmolality of at least about 200 mOsm/kg and a pH inthe range of about 6 to about 9;

(b) packaging the solution and the ophthalmic device in a mannerpreventing contamination of the device by microorganisms; and

(c) sterilizing the packaged solution and ophthalmic device.

The aqueous packaging solutions of the present invention containing atleast tris(hydroxymethyl)aminomethane or a salt thereof result in abuffering system which provides a better stability profile andperformance characteristics for actives such as hyaluronic acid as wellas manufacturing advantages.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows the bar graph of the CBCA for the packaged lenses ofExamples 32-34.

DETAILED DESCRIPTION

The present invention provides a packaging system for the storage ofophthalmic devices intended for direct contact with body tissue or bodyfluid. As used herein, the term “ophthalmic device” refers to devicesthat reside in or on the eye. These lenses can provide opticalcorrection, wound care, drug delivery, diagnostic functionality orcosmetic enhancement or effect or a combination of these properties.Representative examples of such devices include, but are not limited to,soft contact lenses, e.g., a soft, hydrogel lens; soft, non-hydrogellens and the like, hard contact lenses, e.g., a hard, gas permeable lensmaterial and the like, intraocular lenses, overlay lenses, ocularinserts, optical inserts and the like. As is understood by one skilledin the art, a lens is considered to be “soft” if it can be folded backupon itself without breaking. Any material known to produce anophthalmic device including a contact lens can be used herein.

The ophthalmic device will be immersed in an aqueous packaging solutionand stored in a packaging system according to the present invention.Generally, a packaging system for the storage of the ophthalmic deviceaccording to the present invention includes at least a sealed containercontaining one or more unused ophthalmic devices as describedhereinabove immersed in an aqueous packaging solution. Preferably, thesealed container is a hermetically sealed blister-pack, in which aconcave well containing the ophthalmic device is covered by a metal orplastic sheet adapted for peeling in order to open the blister-pack. Thesealed container may be any suitable generally inert packaging materialproviding a reasonable degree of protection to the lens, preferably aplastic material such as polyalkylene, PVC, polyamide, and the like.

In general, the aqueous packaging solution will contain at leasttris(hydroxymethyl)aminomethane(2-amino-2-(hydroxymethyl)propane-1,3-diol), (also known astromethamine, and commonly referred to as tris, tris buffer, trizma ortris base) or a salt thereof. In one preferred embodiment, the firstcomponent is tris(hydroxymethyl)aminomethane in the HCl form.

In one embodiment, the tris(hydroxymethyl)aminomethane or a salt thereofis present in the aqueous packaging solution according to the presentinvention in an amount ranging from about 0.001 to about 1 wt. %, basedon the total weight of the aqueous packaging solution. In anotherembodiment, the tris(hydroxymethyl)aminomethane or salt thereof ispresent in the aqueous packaging solution according to the presentinvention in an amount ranging from about 0.05 to about 1 wt. %, basedon the total weight of the aqueous packaging solution.

In one embodiment, the packaging solution for use in the packagingsystem according to the present invention can further comprise one ormore additional buffer agents. Suitable one or more additional bufferagents include, for example, phosphate buffer agents, borate bufferagents, citrate buffer agents, and the like. A suitable phosphate bufferagent can be any known phosphate buffer agents. In one embodiment, thephosphate buffer agent comprises one or more of sodium hydrogenphosphate monobasic, sodium hydrogen phosphate dibasic, potassiumhydrogen phosphate monobasic and potassium hydrogen phosphate dibasicand any suitable hydrate thereof, e.g., monohydrate and heptahydrate. Asuitable borate buffer agent can be any known borate buffer agents. Inone embodiment, the borate buffer agent comprises one or more of boricacid and sodium borate. A suitable citrate buffer agent can be any knowncitrate buffer agents. In one embodiment, the citrate buffer agentcomprises one or more of citric acid and sodium citrate.

In one embodiment, the one or more additional buffer agents are presentin the packaging solution in an amount ranging from about 0.001 to about2 wt. %, based on the total weight of the packaging solution. In oneembodiment, the phosphate buffer agent is present in the packagingsolution in an amount ranging from about 0.001 to about 2 wt. %, basedon the total weight of the packaging solution.

In one embodiment, the packaging solution for use in the packagingsystem according to the present invention can further comprise one ormore polysaccharides. In one embodiment, a polysaccharide comprises ananionic polysaccharide. Suitable anionic polysaccharides include, forexample, hyaluronic acid or a salt thereof, e.g., sodium hyaluronate orpotassium hyaluronate, chondroitin sulfate, chitosan, aloe vera, andcarboxymethylcellulose. In one embodiment, a polysaccharide comprises anon-ionic polysaccharide. Suitable non-ionic polysaccharides include,for example, hemicellulose, hydroxypropyl methyl cellulose,methylcellulose, and ethylcellulose.

In one embodiment, the one or more polysaccharides are present in thepackaging solution in an amount ranging from about 0.001 to about 10 wt.%, based on the total weight of the packaging solution.

In one embodiment, the packaging solution for use in the packagingsystem according to the present invention can further comprise one ormore non-ionic surfactants. In one embodiment, one or more non-ionicsurfactants can include, for example, one or more end terminalfunctionalized surfactants. A suitable end terminal functionalizedsurfactant includes, by way of example, one or more end terminalfunctionalized polyethers. Useful polyethers to be end terminalfunctionalized comprise one or more chains or polymeric components whichhave one or more (—O—R—) repeats units wherein R is an alkylene orarylene group having 2 to about 6 carbon atoms. The polyethers may bederived from block copolymers formed from different ratio components ofethylene oxide (EO) and propylene oxide (PO). Such polyethers and theirrespective component segments may include different attached hydrophobicand hydrophilic chemical functional group moieties and segments.

A representative example of a suitable polyether which can be endterminal functionalized is a poloxamer block copolymer. One specificclass of poloxamer block copolymers are those available under thetrademark Pluronic (BASF Wyandotte Corp., Wyandotte, Mich.). Poloxamersinclude Pluronics and reverse Pluronics. Pluronics are a series of ABAblock copolymers composed of poly(ethylene oxide)-poly(propyleneoxide)-poly(ethylene oxide) blocks as generally represented in FormulaVII:

HO(C₂H₄O)_(a)(C₃H₆O)_(b)(C₂H₄O)_(a)H  (VII)

wherein a is independently at least 1 and b is at least 1.

Reverse Pluronics are a series of BAB block copolymers, respectivelycomposed of poly(propylene oxide)-poly(ethylene oxide)-poly(propyleneoxide) blocks as generally represented in Formula VIII:

HO(C₃H₆O)_(b)(C₂H₄O)_(a)(C₃H₆O)_(b)H  (VIII)

wherein a is at least 1 and b is independently at least 1. Thepoly(ethylene oxide), PEO, blocks are hydrophilic, whereas thepoly(propylene oxide), PPO, blocks are hydrophobic in nature. Thepoloxamers in each series have varying ratios of PEO and PPO whichultimately determines the hydrophilic-lipophilic balance (HLB) of thematerial, i.e., the varying HLB values are based upon the varying valuesof a and b, a representing the number of hydrophilic poly(ethyleneoxide) units (PEO) being present in the molecule and b representing thenumber of hydrophobic poly(propylene oxide) units (PPO) being present inthe molecule.

Poloxamers and reverse poloxamers have terminal hydroxyl groups that canbe terminal functionalized. An example of a terminal functionalizedpoloxamer and as discussed herein below is poloxamer dimethacrylate(e.g., Pluronic® F127 dimethacrylate) as disclosed in U.S. PatentApplication Publication No. 2003/0044468 and U.S. Pat. No. 9,309,357.Other examples include glycidyl-terminated copolymers of polyethyleneglycol and polypropylene glycol as disclosed in U.S. Pat. No. 6,517,933.

Another example of a suitable polyether which can be end terminalfunctionalized is a poloxamine block copolymer. While the poloxamers andreverse poloxamers are considered to be difunctional molecules (based onthe terminal hydroxyl groups), the poloxamines are in a tetrafunctionalform, i.e., the molecules are tetrafunctional block copolymersterminating in primary hydroxyl groups and linked by a central diamine.One specific class of poloxamine block copolymers are those availableunder the trademark Tetronic (BASF). Poloxamines include Tetronic andreverse Tetronics. Poloxamines have the following general structure ofFormula IX:

wherein a is independently at least 1 and b is independently at least 1.

The poloxamer and/or poloxamine is functionalized to provide the desiredreactivity at the end terminal of the molecule. The functionality can bevaried and is determined based upon the intended use of thefunctionalized PEO- and PPO-containing block copolymers. That is, thePEO- and PPO-containing block copolymers are reacted to provide endterminal functionality that is complementary with the intended deviceforming monomeric mixture. The term block copolymer as used herein shallbe understood to mean a poloxamer and/or poloxamine as having two ormore blocks in their polymeric backbone(s).

In one embodiment, the one or more non-ionic surfactants are present inthe packaging solution in an amount ranging from about 0.001 to about 10wt. %, based on the total weight of the packaging solution.

In one embodiment, the packaging solution according to the presentinvention can further include one or more additives such as, forexample, a poloxamer di(meth)acrylate, a reverse poloxamerdi(meth)acrylate, a poloxamine di(meth)acrylate, a reverse poloxaminedi(meth)acrylate, Mirj and Birj.

In one embodiment, the packaging solution according to the presentinvention can further include one or more additives such as, forexample, trehalose L-Carnitine, erythritol, vitamin E TPGS (tocopherylpolyethylene glycol succinate), and the like.

In one embodiment, the packaging solution according to the presentinvention can further include one or more additives such as, forexample, NaCl, KCl; amino taurine, glycine, diglycine, alanine;mannitol, sorbitol and propylene glycol.

The packaging solutions according to the present invention arephysiologically compatible. Specifically, the solution must be“ophthalmically safe” for use with a lens such as a contact lens,meaning that a contact lens treated with the solution is generallysuitable and safe for direct placement on the eye without rinsing, thatis, the solution is safe and comfortable for daily contact with the eyevia a contact lens that has been wetted with the solution. Anophthalmically safe solution has a tonicity and pH that is compatiblewith the eye and includes materials, and amounts thereof, that arenon-cytotoxic according to ISO standards and U.S. Food & DrugAdministration (FDA) regulations.

The packaging solution should also be sterile in that the absence ofmicrobial contaminants in the product prior to release must bestatistically demonstrated to the degree necessary for such products.The liquid media useful in the present invention are selected to have nosubstantial detrimental effect on the lens being treated or cared forand to allow or even facilitate the present lens treatment ortreatments. The liquid media are preferably aqueous-based. Aparticularly useful aqueous liquid medium is that derived from saline,for example, a conventional saline solution or a conventional bufferedsaline solution.

The pH of the present solutions is maintained within the range of about6 to about 9, and preferably about 6.5 to about 7.8. As mentioned above,additional buffer may optionally be added, such as boric acid, sodiumborate, potassium citrate, sodium citrate, citric acid, sodiumbicarbonate, various mixed phosphate buffers (including combinations ofNa₂HPO₄, NaH₂PO₄ and KH₂PO₄), hydrates thereof and the like and mixturesthereof. Generally, buffers will be used in amounts ranging from about0.05 to about 2.5 percent by weight, and preferably from about 0.1 toabout 1.5 percent by weight of the solution. However, according tocertain embodiments, tris(hydroxymethyl)aminomethane, or salts thereof,function as the sole buffer.

Typically, the solutions of the present invention are also adjusted withtonicity agents, to approximate the osmotic pressure of normal lacrimalfluids which is equivalent to a 0.9 percent solution of sodium chlorideor 2.5 percent of glycerol solution. The solutions are madesubstantially isotonic with physiological saline used alone or incombination, otherwise if simply blended with sterile water and madehypotonic or made hypertonic the lenses will lose their desirableoptical parameters. Correspondingly, excess saline may result in theformation of a hypertonic solution which will cause stinging and eyeirritation.

Examples of suitable tonicity adjusting agents include, but are notlimited to, sodium and potassium chloride, dextrose, glycerin, calciumand magnesium chloride and the like and mixtures thereof. These agentsare typically used individually in amounts ranging from about 0.01 toabout 2.5% w/v and preferably from about 0.2 to about 1.5% w/v.Preferably, the tonicity agent will be employed in an amount to providea final osmotic value of at least about 200 mOsm/kg, or from about 200to about 400 mOsm/kg, or from about 250 to about 350 mOsm/kg, or fromabout 280 to about 320 mOsm/kg.

If desired, one or more additional components can be included in thepackaging solution. Such additional component or components are chosento impart or provide at least one beneficial or desired property to thepackaging solution. Such additional components may be selected fromcomponents which are conventionally used in one or more ophthalmicdevice care compositions. Examples of such additional components includecleaning agents, wetting agents, nutrient agents, sequestering agents,viscosity builders, contact lens conditioning agents, antioxidants, andthe like and mixtures thereof. These additional components may each beincluded in the packaging solutions in an amount effective to impart orprovide the beneficial or desired property to the packaging solutions.For example, such additional components may be included in the packagingsolutions in amounts similar to the amounts of such components used inother, e.g., conventional, contact lens care products.

Useful sequestering agents include, but are not limited to, disodiumethylene diamine tetraacetate, alkali metal hexametaphosphate, citricacid, sodium citrate and the like and mixtures thereof.

Useful viscosity builders include, but are not limited to, hydroxyethylcellulose, hydroxymethyl cellulose, polyvinyl pyrrolidone, polyvinylalcohol and the like and mixtures thereof.

Useful antioxidants include, but are not limited to, sodiummetabisulfite, sodium thiosulfate, N-acetylcysteine, butylatedhydroxyanisole, butylated hydroxytoluene and the like and mixturesthereof.

The method of packaging and storing an ophthalmic device such as acontact lens according to the present invention includes at leastpackaging an ophthalmic device immersed in the aqueous packagingsolution described above. The method may include immersing theophthalmic device in an aqueous packaging solution prior to delivery tothe customer/wearer, directly following manufacture of the contact lens.Alternately, the packaging and storing in the solution of the presentinvention may occur at an intermediate point before delivery to theultimate customer (wearer) but following manufacture and transportationof the lens in a dry state, wherein the dry lens is hydrated byimmersing the lens in the packaging solution. Consequently, a packagefor delivery to a customer may include a sealed container containing oneor more unused contact lenses immersed in an aqueous packaging solutionaccording to the present invention.

In one embodiment, the steps leading to the present ophthalmic devicepackaging system includes (1) molding an ophthalmic device in a moldcomprising at least a first and second mold portion, (2) hydrating andcleaning the device in a container comprising at least one of the moldportions, (3) introducing the packaging solution with the copolymer intothe container with the device supported therein, and (4) sealing thecontainer. Preferably, the method also includes the step of sterilizingthe contents of the container. Sterilization may take place prior to, ormost conveniently after, sealing of the container and may be effected byany suitable method known in the art, e.g., by autoclaving of the sealedcontainer at temperatures of about 120° C. or higher.

The following examples are provided to enable one skilled in the art topractice the invention and are merely illustrative of the invention. Theexamples should not be read as limiting the scope of the invention asdefined in the claims.

Various packaging solution were formed as discussed below andcharacterized by a standard testing procedure such as:

Contact Angle (CBCA): Captive bubble contact angle data was collected ona First Ten Angstroms FTA-1000 drop Shape Instrument. All samples wererinsed in HPLC grade water prior to analysis in order to removecomponents of the packaging solution from the sample surface. Prior todata collection the surface tension of the water used for allexperiments was measured using the pendant drop method. In order for thewater to qualify as appropriate for use, a surface tension value of70-72 dynes/cm was expected. All lens samples were placed onto a curvedsample holder and submerged into a quartz cell filled with HPLC gradewater. Advancing and receding captive bubble contact angles werecollected for each sample. The advancing contact angle is defined as theangle measured in water as the air bubble is retracting from the lenssurface (water is advancing across the surface). All captive bubble datawas collected using a high speed digital camera focused onto thesample/air bubble interface. The contact angle was calculated at thedigital frame just prior to contact line movement across the sample/airbubble interface. The receding contact angle is defined as the anglemeasured in water as the air bubble is expanding across the samplesurface (water is receding from the surface).

In the example, the following abbreviations are used.

CMC: Carboxymethyl cellulose polymer having a viscosity of 100 to 1000cPs and represented by the structure:

HPMC: Hydroxypropylmethyl cellulose polymer having a viscosity of about2500 to about 5000 cPs and represented by the structure:

PDMA-C18-RAFT Surfactant: a poly(dimethylacrylamide) polymer having anumber average molecular weight of about 10400 to about 65400, a weightaverage molecular weight of about 10700 to about 92050 Da and apolydispersity of about 1.03 to about 1.41, and is represented by thefollowing structure:

wherein R is CN, OH or H.

PVP-C18-RAFT Surfactant: a polyvinyl pyrrolidone polymer having a numberaverage molecular weight of about 5600 to about 31300, a weight averagemolecular weight of about 6400 to about 41300 Da and a polydispersity ofabout 1.14 to about 1.32, and is represented by the following structure:

wherein R is CN, OH or H.

PDMA-VDO: a PolyDMA-co-vinyl-4,4-Dimethyl-2-oxazoline-5-one where m is10 to 50 and n is 10 to 50 and having a number average molecular weight(Mn) from about 10,000 to about 50,000 and a weight average molecularweight (Mw) from about 15,000 to about 100,000 and a polydispersity ofabout 1.2 to about 2.0

Poly(acrylic acid)-grafted-poly(ethylene glycol) (PAA-g-PEG): a graftedpolymer wherein the number average molecular weight of the PAA backboneis 60 kDa, the number average molecular weight of the PEG side chains is2 kDa and the PEG substitution is about 78%. The PAA-g-PEG graftedpolymer is represented by the following structure:

wherein m is 10 to 50, a is 10 to 50 and b is 10 to 50.

Poly(acrylic acid)-co-poly(ethylene glycol) monoether acrylate(PAA-co-PEG): a copolymer having the structure:

wherein n is 10-50, a is 10 to 50 and b is 10 to 50.

Poly(dimethylacrylamide)-co-poly(ethylene glycol methacrylate)(PDMA-co-PEGMA): a copolymer having a number average molecular weight ofabout 15 to about 80 kDa, a weight average molecular weight of about 19to about 100 kDa and a polydispersity of about 1.30 to about 1.45. ThePDMA-co-PEGMA copolymer is represented by the following structure:

Poly(acrylic acid)-2-dimethyl ethylenediamine (PAA-2-dimethylethylenediamine): a polymer having the structure:

wherein m is 10 to 50.

Poly(acrylic acid)-ethylenediamine (boc deprotected)(PAA-ethylenediamine (boc deprotected): a deprotected polymer having thestructure:

wherein m is 10 to 50.

Tetronic 1107: a block copolymer surfactant

Example 1

A packaging solution is made by mixing the following components in therespective amounts listed in Table 1.

TABLE 1 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 SodiumChloride 0.720 pH 7.54 Osmolality 303

Example 2

A packaging solution is made by mixing the following components in therespective amounts listed in Table 2.

TABLE 2 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.780 pH 7.54 Osmolality 310

Example 3

A packaging solution is made by mixing the following components in therespective amounts listed in Table 3.

TABLE 3 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.780 Tetronic 1107 0.50 pH 7.54 Osmolality 310

Example 4

A packaging solution is made by mixing the following components in therespective amounts listed in Table 4.

TABLE 4 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.780 Tetronic 1107 0.50 Trehalose 0.20 pH 7.40-7.60 Osmolality320-370

Example 5

A packaging solution is made by mixing the following components in therespective amounts listed in Table 5.

TABLE 5 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.780 Tetronic 1107 0.50 Erythritol 0.20-0.50 pH 7.40-7.60Osmolality 320-370

Example 6

A packaging solution is made by mixing the following components in therespective amounts listed in Table 6.

TABLE 6 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 Erythritol 0.20-0.50 pH7.40-7.60 Osmolality 320-370

Example 7

A packaging solution is made by mixing the following components in therespective amounts listed in Table 7.

TABLE 7 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.580 Propylene Glycol 0.300 Tetronic 1107 0.50 Erythritol0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 8

A packaging solution is made by mixing the following components in therespective amounts listed in Table 8.

TABLE 8 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 L-Carnitine 0.20-0.50pH 7.40-7.60 Osmolality 320-370

Example 9

A packaging solution is made by mixing the following components in therespective amounts listed in Table 9.

TABLE 9 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 L-Carnitine 0.20-0.50Erythritol 0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 10

A packaging solution is made by mixing the following components in therespective amounts listed in Table 10.

TABLE 10 Ingredient % W/V Tris HCl 0.320 Sodium Borate 0.080 PotassiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 L-Carnitine 0.20-0.50Erythritol 0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 11

A packaging solution is made by mixing the following components in therespective amounts listed in Table 11.

TABLE 11 Ingredient % W/V Tris HCl 0.320 Sodium Phosphate, dibasic 0.100Potassium Chloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 L-Carnitine0.20-0.50 Erythritol 0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 12

A packaging solution is made by mixing the following components in therespective amounts listed in Table 12.

TABLE 12 Ingredient % W/V Tris HCl 0.530 Trizma Base 0.080 PotassiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 Hyaluronic acid 0.05Erythritol 0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 13

A packaging solution is made by mixing the following components in therespective amounts listed in Table 13.

TABLE 13 Ingredient % W/V Tris HCl 0.320 Sodium Citrate 0.150 SodiumChloride 0.580 Glycerin 0.300 Tetronic 1107 0.50 Hyaluronic acid 0.05Erythritol 0.20-0.50 pH 7.40-7.60 Osmolality 320-370

Example 14

A packaging solution is made by mixing the following components in therespective amounts listed in Table 14.

TABLE 14 Ingredient % W/W Trizma HCl 11.018 Trizma Base 2.045 SodiumChloride 0.502 Purified Water 86.435 Viscosity 1.50-1.55 pH 7.45Osmolality 1025

Example 15

A packaging solution is made by mixing the following components in therespective amounts listed in Table 15.

TABLE 15 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 Viscosity 1.13-1.30 pH 7.55Osmolality 272

Example 16

A packaging solution is made by mixing the following components in therespective amounts listed in Table 16.

TABLE 16 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 CMC 0.05-0.25 Viscosity 1.42-3.37pH 7.5-7.6 Osmolality 271-274

Example 17

A packaging solution is made by mixing the following components in therespective amounts listed in Table 17.

TABLE 17 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PDMA-C18 0.05 Viscosity 1.20-1.34pH 7.55 Osmolality 273

Example 18

A packaging solution is made by mixing the following components in therespective amounts listed in Table 18.

TABLE 18 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680PDMA-co-vinyl-4,4-dimethyl-2-oxazoline-5-one 0.05 Viscosity 1.20-1.28 pH7.51 Osmolality 270

Example 19

A packaging solution is made by mixing the following components in therespective amounts listed in Table 19.

TABLE 19 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PVP-C18 0.05 Viscosity 1.24-1.33 pH7.53 Osmolality 269

Example 20

A packaging solution is made by mixing the following components in therespective amounts listed in Table 20.

TABLE 20 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 HPMC 0.05-0.5  Viscosity 1.1-1.8 pH7.1-7.8 Osmolality 200-400

Example 21

A packaging solution is made by mixing the following components in therespective amounts listed in Table 21.

TABLE 21 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PAA-g-PEG 0.02-0.5  Viscosity1.1-1.8 pH 7.1-7.5 Osmolality 200-400

Example 22

A packaging solution is made by mixing the following components in therespective amounts listed in Table 22.

TABLE 22 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PAA-co-PEG 0.02-0.5  Viscosity1.1-1.8 pH 7.1-7.5 Osmolality 200-400

Example 23

A packaging solution is made by mixing the following components in therespective amounts listed in Table 23.

TABLE 23 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PDMA-co-PEG400MA 0.02-0.5 Viscosity 1.1-1.8 pH 7.1-7.5 Osmolality 200-400

Example 24

A packaging solution is made by mixing the following components in therespective amounts listed in Table 24.

TABLE 24 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 PAA-amine 0.02-0.5  Viscosity1.1-1.8 pH 7.1-7.5 Osmolality 200-400

Example 25

A packaging solution is made by mixing the following components in therespective amounts listed in Table 25.

TABLE 25 Ingredient % W/W Trizma HCl 0.627 Trizma Base 0.116 SodiumChloride 0.577 Purified Water 98.680 Tetronic 1107 0.05-0.5  Viscosity1.1-1.8 pH 7.1-7.5 Osmolality 200-400

Comparative Example A

A borated buffer packaging solution (BBS) was made by mixing thefollowing components in the respective amounts listed in Table 26.

TABLE 26 Ingredient % W/W Sodium Chloride 0.459 Sodium Borate 0.125Boric Acid 1.148 Purified Water 98.83 Viscosity  1.0-1.25 pH 7.1-7.4Osmolality 330-350

Comparative Example B

A packaging solution was made by adding 0.5 wt. % Poloxamine 1107 to theBBS solution of Comparative Example A.

Example 26

A packaging solution was made by adding 0.25 wt. % CMC to the BBSsolution of Comparative Example A.

Example 27

A packaging solution was made by adding 0.05 wt. % CMC to the BBSsolution of Comparative Example A.

Example 28

A packaging solution was made by adding 0.05 wt. % PDMA-C18 to the BBSsolution of Comparative Example A.

Example 29

A packaging solution was made by adding 0.05 wt. % PDMA-VDO to the BBSsolution of Comparative Example A.

Example 30

A packaging solution was made by adding 0.05 wt. % PVP-C18 to the BBSsolution of Comparative Example A.

Example 31

A nesofilcon A (BioTrue) lens was packaged in each of the packagingsolutions of Comparative Examples A and B and Examples 26-30 andautoclaved for 30 min at 121° C.

Example 32

A samfilcon A (Ultra) lens was packaged in each of the packagingsolutions of Comparative Examples A and B and Examples 26-30 andautoclaved for 30 min at 121° C.

Example 33

A new silicone daily disposable (Crystal RDF2081-43) lens was packagedin each of the packaging solutions of Comparative Examples A and B andExamples 26-30 and autoclaved for 30 min at 121° C.

Testing

Each of the packaged lenses of Examples 31-33 were removed from thepackage after and then measured for the lens diameters as set forthbelow in Tables 28-30.

TABLE 27 Crystal RDF2081-43 lens diameter data Solution Diameter (mm)Comp. Ex. A 15.52 Comp. Ex. B 15.591 Example 26 15.471 Example 27 15.545Example 28 15.566 Example 29 15.49 Example 30 15.327

TABLE 28 BioTrue lens diameter data Solution Diameter (mm) Comp. Ex. A14.300 Comp. Ex. B 14.013 Example 26 14.364 Example 27 14.339 Example 2814.368 Example 29 14.344 Example 30 14.295

TABLE 29 Ultra lens diameter data Solution Diameter (mm) Comp. Ex. A14.327 Comp. Ex. B 14.238 Example 26 14.620 Example 27 14.221 Example 2814.383 Example 29 14.530 Example 30 14.366

Each of the packaged lenses of Examples 31-33 were removed from thepackaging solution after and then measured for CBCA. The results of thedata are set forth in FIG. 1.

Examples 34 and 35 and Comparative Example C

A packaging solution was made by mixing the following components in therespective amounts listed in Table 30.

TABLE 30 Comp. Ingredients EXAMPLE 34 EXAMPLE 35 Ex. C Tris HCl, % wt/wt0.130 0.530 — Trizma base, % wt/wt — 0.075 — Sodium Phosphate 0.09 — —Dibasic Heptahydrate, % wt/wt Potassium Chloride, 0.9 0.8 — % wt/wtGlycerin, % wt/wt 0.73 0.55 0.55 Erythritol, % wt/wt 0.300 0.3 0.3Tetronic 1107, % wt/wt 0.50 0.500 0.500 Water QS to 100% QS to 100% QSto 100% pH 7.40 7.55 Osmolarity 365 359

Examples 36 and 37 and Comparative Example D

A packaging solution was made by mixing the following components in therespective amounts listed in Table 31.

TABLE 31 Comp. Ingredients EXAMPLE 36 EXAMPLE 37 Ex. D Tris HCl, % wt/wt0.130 0.530 — Trizma base, % wt/wt — 0.075 — Sodium Phosphate 0.09 — —Dibasic Heptahydrate, % wt/wt Potassium Chloride, 0.9 0.8 — % wt/wtGlycerin, % wt/wt 0.73 0.55 0.55 Erythritol, % wt/wt 0.300 0.3 0.3Tetronic 1107, % wt/wt 0.50 0.500 0.500 Chondroitin Sulfate, 0.50 0.500.50 % wt/wt water QS to 100% QS to 100% QS to 100% pH 7.40 7.55 —Osmolality 365 359 —

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore, the above description shouldnot be construed as limiting, but merely as exemplifications ofpreferred embodiments. For example, the functions described above andimplemented as the best mode for operating the present invention are forillustration purposes only. Other arrangements and methods may beimplemented by those skilled in the art without departing from the scopeand spirit of this invention. Moreover, those skilled in the art willenvision other modifications within the scope and spirit of the featuresand advantages appended hereto.

What is claimed is:
 1. A packaging system for the storage of an ophthalmic device comprising a sealed container that contains an unused, ophthalmic device in an aqueous packaging solution comprising tris(hydroxymethyl)aminomethane or a salt thereof; wherein the solution has an osmolality of at least about 200 mOsm/kg and a pH in the range of about 6 to about
 9. 2. The packaging system of claim 1, wherein the tris(hydroxymethyl)aminomethane or a salt thereof is tris(hydroxymethyl)aminomethane hydrochloride.
 3. The packaging system of claim 1, wherein the packaging solution comprises about 0.001 to about 1 wt. %, based on the total weight of the aqueous packaging solution, of the tris(hydroxymethyl)aminomethane or salt thereof.
 4. The packaging system of claim 1, wherein the packaging solution further comprises one or more buffer agents.
 5. The packaging system of claim 4, wherein the one or more buffer agents are selected from the group consisting of a phosphate buffer agent, a borate buffer agent, a citrate buffer agent, MOPS buffer agent and mixtures thereof.
 6. The packaging system of claim 4, wherein the packaging solution comprises about 0.001 to about 2 wt. %, based on the total weight of the aqueous packaging solution, of the one or more buffer agents.
 7. The packaging system of claim 1, wherein the packaging solution further comprises one or more of a borate compound, sodium phosphate, and sodium citrate.
 8. The packaging system of claim 1, wherein the packaging solution further comprises a polysaccharide.
 9. The packaging system of claim 8, wherein the polysaccharide comprises an anionic polysaccharide or a non-ionic polysaccharide.
 10. The packaging system of claim 8, wherein the polysaccharide comprises one or more of hyaluronic acid or a salt thereof, chondroitin sulfate, chitosan, aloe vera, carboxymethylcellulose, hemicellulose, hydroxypropyl methyl cellulose, methylcellulose, and ethylcellulose.
 11. The packaging system of claim 1, wherein the packaging solution further comprises one or more of hyaluronic acid, sodium hyaluronate, and potassium hyaluronate.
 12. The packaging system of claim 1, wherein the packaging solution further comprises one or more additives selected from the group consisting of an antioxidant, a non-ionic surfactant, an osmolyte and mixtures thereof.
 13. The packaging system of claim 1, wherein the packaging solution further comprises one or more additives selected from the group consisting of L-Carnitine, erythritol, and vitamin E TPGS (tocopheryl polyethylene glycol succinate).
 14. The packaging system of claim 1, wherein the packaging solution further comprises one or more additives selected from the group consisting of a poloxamer di(meth)acrylate, a reverse poloxamer di(meth)acrylate, a poloxamine di(meth)acrylate, a reverse poloxamine di(meth)acrylate, Mirj and Birj.
 15. The packaging system of claim 1, wherein the packaging solution further comprises one or more additives selected from the group consisting of NaCl, KCl; taurine, glycine, diglycine, alanine; mannitol, sorbitol and propylene glycol.
 16. The packaging system of claim 1, wherein the ophthalmic device is a contact lens.
 17. The packaging system of claim 1, wherein the ophthalmic device is a hydrogel or silicone hydrogel contact lens.
 18. The packaging system of claim 1, wherein the solution does not contain an effective disinfecting amount of a disinfecting agent.
 19. The packaging system of claim 1, wherein the solution does not contain a germicide compound.
 20. The packaging system of claim 1, wherein the package is heat sterilized subsequent to sealing of the package.
 21. A method of preparing a package comprising a storable, sterile ophthalmic device, the method comprising: (a) immersing an ophthalmic device in an aqueous packaging solution comprising tris(hydroxymethyl)aminomethane or a salt thereof, wherein the solution has an osmolality of at least about 200 mOsm/kg and a pH in the range of about 6 to about 9; (b) packaging the solution and the ophthalmic device in a manner preventing contamination of the device by microorganisms; and (c) sterilizing the packaged solution and ophthalmic device.
 22. The method of claim 21, wherein the tris(hydroxymethyl)aminomethane or a salt thereof is tris(hydroxymethyl)aminomethane hydrochloride.
 23. The method of claim 21, wherein the packaging solution comprises about 0.001 to about 2 wt. %, based on the total weight of the aqueous packaging solution, of the tris(hydroxymethyl)aminomethane or salt thereof.
 24. The method of claim 21, wherein the packaging solution further comprises one or more buffer agents.
 25. The method of claim 24, wherein the one or more buffer agents are selected from the group consisting of a phosphate buffer agent, a borate buffer agent, a citrate buffer agent, a (3-(N-morpholino)propanesulfonic acid) buffer agent and mixtures thereof.
 26. The method of claim 24, wherein the packaging solution comprises about 0.001 to about 2 wt. %, based on the total weight of the aqueous packaging solution, of the one or more buffer agents.
 27. The method of claim 21, wherein the packaging solution further comprises one or more of a borate compound, sodium phosphate, and sodium citrate.
 28. The method of claim 21, wherein the packaging solution further comprises a polysaccharide.
 29. The method of claim 28, wherein the polysaccharide comprises an anionic polysaccharide or a non-ionic polysaccharide.
 30. The method of claim 28, wherein the polysaccharide comprises one or more of hyaluronic acid or a salt thereof, chondroitin sulfate, chitosan, aloe vera, carboxymethylcellulose, hemicellulose, hydroxypropyl methyl cellulose, methylcellulose, and ethylcellulose.
 31. The method of claim 21, wherein the packaging solution further comprises one or more of hyaluronic acid, sodium hyaluronate, and potassium hyaluronate.
 32. The method of claim 21, wherein the packaging solution further comprises one or more additives selected from the group consisting of an antioxidant, a non-ionic surfactant, an osmolyte and mixtures thereof.
 33. The method of claim 21, wherein the packaging solution further comprises one or more additives selected from the group consisting of L-Carnitine, erythritol, and vitamin E TPGS (tocopheryl polyethylene glycol succinate).
 34. The method of claim 21, wherein the packaging solution further comprises one or more additives selected from the group consisting of a poloxamer di(meth)acrylate, a reverse poloxamer di(meth)acrylate, a poloxamine di(meth)acrylate, a reverse poloxamine di(meth)acrylate, Mirj and Birj.
 35. The method of claim 21, wherein the packaging solution further comprises one or more additives selected from the group consisting of NaCl, KCl; taurine, glycine, diglycine, alanine; mannitol, sorbitol and propylene glycol.
 36. The method of claim 21, wherein the ophthalmic device is a contact lens.
 37. The method of claim 21, wherein the ophthalmic device is a silicone hydrogel contact lens.
 38. The method of claim 21, wherein the packaging solution does not contain an effective disinfecting amount of a disinfecting agent.
 39. The method of claim 21, wherein the packaging solution does not contain a germicide compound.
 40. The method of claim 21, wherein the packaging solution further comprises one or more additives selected from the group consisting of taurine, carboxymethyl cellulose, hydroxypropylmethyl cellulose, a poly(dimethylacrylamide) polymer having a number average molecular weight of about 10400 to about 65400 and represented by the following structure:

wherein R is CN, OH or H; a polyvinyl pyrrolidone polymer having a number average molecular weight of about 5600 to about 31300 and represented by the following structure:

wherein R is CN, OH or H, a poly(acrylic acid)-grafted-poly(ethylene glycol) polymer represented by the following structure:

wherein m is 10 to 50, a is 10 to 50 and b is 10 to 50, a poly(acrylic acid)-co-poly(ethylene glycol) monoether acrylate copolymer represented by the structure:

wherein n is 10 to 50, a is 10 to 50 and b is 10 to 50, a poly(dimethylacrylamide)-co-poly(ethylene glycol methacrylate) copolymer represented by the following structure:

wherein m is 10 to 50, and n is 10 to 50, a poly(acrylic acid)-2-dimethyl ethylenediamine polymer having the structure:

wherein m is 10 to 50, a poly(acrylic acid)-ethylenediamine deprotected polymer having the structure:

wherein m is 10 to 50, and polyDMA-co-vinyl-4,4-Dimethyl-2-oxazoline-5-one polymer represented by the structure:

wherein m is 10 to 50 and n is 10 to
 50. 